Ticlopidine抑制腫瘤壞死因子-α刺激人類臍帶內皮細胞所分泌的單核球趨化激素-1與介白質素-8之探討

Ticlopidine Inhibits Monocyte Chemoattractant Protein-1 and Interleukin-8 Expression in TNF--α Stimulated Human Umbilical Vein Endothelial Cells

戴子怡(Tzu-Yi Tai)

指導教授 ： 呂思潔

臺北醫學大學/醫學院/細胞及分子生物研究所/碩士(2002年)

摘要

Ticlopidine抑制腫瘤壞死因子-α刺激人類臍帶內皮細胞所分泌的 單核球趨化激素-1與介白質素-8之探討 戴子怡 動脈硬化是一種發炎性的疾病會影響人類的健康，當動脈管壁上的內皮細胞層受到損傷時會導致血液中的單核球及T-淋巴球匯集至血管管壁內是為動脈硬化初期發展過程的主要特徵之一，而趨化素為單核球及T-淋巴球遷移作用的調控者其中就包括有單核球趨化素-1;單核球趨化素-1會表現在動脈硬化損傷部位內而導致單核球與T-淋巴球過量地聚集，而IL-8在過去有研究指出在動脈硬化損傷部位內有IL-8的存在以及從動脈硬化的患者體內分離出來的巨噬細胞會表現IL-8。ticlopidine是一種抗血栓的藥物可用來預防治療動脈硬化，但是有關於ticlopidine的作用機制尚未清楚地了解。 在本研究中我們主要探討ticlopidine對於受到TNF-α刺激的HUVEC所表現的單核球趨化素-1 (MCP-1) 和介白質素-8 (IL-8)之影響。結果顯示ticlopidine可抑制TNF-α 所誘導MCP-1和IL-8的蛋白質及mRNA表現，亦可抑制TNF-α 所誘導VCAM-1的表現。同時Ticlopidine可抑制U937單核球的吸附作用。加入抗MCP-1及抗IL-8抗體都可抑制單核球的吸附作用。此外我們也發現到在U937上有IL-8 receptor CXCR1的存在，而IL-8對於U937具有趨化性的作用。這些結果顯示ticlopidine可抑制受到TNF-α刺激的HUVEC表現MCP-1、IL-8及VCAM-1，為此可能提供了另一項治療機制。

關鍵字

人類臍帶內皮細胞 ； 單核球趨化蛋白-1 ； ticlopidine ； 介白質素-8

並列摘要

Abstract Ticlopidine Inhibits Monocyte Chemoattractant Protein-1 and Interleukin-8 Expression in TNF-α Stimulated Human Umbilical Vein Endothelial Cells Tzu-Yi Tai Atherosclerosis is an inflammatory disease, it can influence human，s heath . Key evidence of atherosclerosis is the initial influx of monocytes and T-lymphocytes into the vessel wall in response to injury to the endothelium. Mediators of this migration are chemokines including monocyte chemoattractant protein-1 (MCP-1). MCP-1 were expressed in human atherosclerotic lesions, cause monocytes、T-lymphocyte into the subendothelial space and lead over collection. IL-8 has been reported in atherosclerotic lesions and circulating macrophages from patients with atherosclerosis. Ticlopidine is an antithrombotic agent which used to prevent atherosclerosis, but its mechanism of action has not yet been completely understood. In this study, the effects of ticlopidine on MCP-1 and IL-8 expression in TNF-α stimulated human umbilical vein endothelial cells (HUVECs) were investigated. We have demonstrated ticlopidine inhibits TNF-α-induced MCP-1 and IL-8 protein and mRNA expression. Ticlopidine inhibits TNF-α-induced VCAM-1 expression. Ticlopidine also inhibits U937 monocytic cell to adhere to HUVECs, the treatment of anti IL-8 and anti MCP-1 antibodies inhibit monocytes adhesion. Besides, we found IL-8 receptor CXCR1 were expressed on U937 cells, and U937 respond chemotactically to CXC chemokine IL-8 in vitro. These results suggest that ticlopidine inhibits MCP-1、IL-8 and VCAM-1 expression in HUVEC stimulated by TNF-α, thereby providing an additional mechanism for therapeutic effect of ticlopidine.

並列關鍵字

HUVECs ； MCP-1 ； ticlopidine ； IL-8

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